Multi-omic analysis of CNS-draining lymph nodes

Supervisors: Paul Klenerman, Adam Al-Diwani, Paul Harrison, Nicholas Provine

Nuffield Department of Medicine and University Department of Psychiatry

Background

Analysis of immunologic and inflammatory changes in the CNS is critical for understanding a range of neurologic, including neurodegenerative, disease. However, it is hampered substantially by issues of access to tissue, especially repeated access. There is increasing evidence that the cervical lymph node chain drains CNS lymph. We have recently shown that fine-needle analysis of cervical chain lymph nodes can provide high resolution data on both the cellular content (by scRNAseq) and soluble molecules (by O-Link and SIMOA), measuring features of relevance to CNS homeostasis and disease. Importantly, delivered by senior radiologist, this procedure is safe and very well tolerated, allowing for repeated measures.

Aims

We intend to expand this FNA protocol to explore key parameters of age, sex, and stability in a range of healthy donors, using 10x scRNASeq/ATACseq and CITE-seq protocols and further proteomic analysis. Having further validated the system and in particular defined the impact of age, we will address multi-omic changes in a well-defined cohort of patients with neurodegenerative disease presenting as Alzheimer’s dementia.

Key outputs

This project will provide an atlas of CNS-draining lymph nodes including the environment of key local soluble mediators and biomarkers. It will provide a key resource for studies of neurodegeneration by generation of a substantial dataset across a range of healthy donors. It will also show proof-of-principle of the utility of such approaches to disease cohorts and potentially generate key data for larger prospective cohort studies using this minimally invasive approach.